CLDN4

Functionⁱ

Plays a major role in tight junction-specific obliteration of the intercellular space.By similarity

GO - Molecular functionⁱ

identical protein binding Source: UniProtKB
structural molecule activity Source: InterPro
transmembrane signaling receptor activity
Source: ProtInc
Traceable author statementⁱ
- 9334247

Complete GO annotation...

GO - Biological processⁱ

calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules Source: UniProtKB
circadian rhythm Source: Ensembl
establishment of skin barrier
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23407391
female pregnancy Source: Ensembl
response to progesterone Source: Ensembl

Complete GO annotation...

Enzyme and pathway databases

Reactomeⁱ	R-HSA-420029. Tight junction interactions.

Reactomeⁱ

R-HSA-420029. Tight junction interactions.

Protein family/group databases

TCDBⁱ	1.H.1.1.6. the claudin tight junction (claudin1) family.

TCDBⁱ

1.H.1.1.6. the claudin tight junction (claudin1) family.

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Claudin-4 Alternative name(s): Clostridium perfringens enterotoxin receptor Short name: CPE-R Short name: CPE-receptor Williams-Beuren syndrome chromosomal region 8 protein
Gene namesⁱ	Name:CLDN4 Synonyms:CPER, CPETR1, WBSCR8
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 7

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:2046. CLDN4.

HGNCⁱ

HGNC:2046. CLDN4.

Subcellular locationⁱ

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 7	CytoplasmicSequence analysis	7
Transmembraneⁱ	8 – 28	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	29 – 81	ExtracellularSequence analysisAdd BLAST	53
Transmembraneⁱ	82 – 102	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	103 – 117	CytoplasmicSequence analysisAdd BLAST	15
Transmembraneⁱ	118 – 138	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	139 – 160	ExtracellularSequence analysisAdd BLAST	22
Transmembraneⁱ	161 – 181	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	182 – 209	CytoplasmicSequence analysisAdd BLAST	28

GO - Cellular componentⁱ

apical plasma membrane Source: Ensembl
apicolateral plasma membrane Source: Ensembl
basal plasma membrane Source: Ensembl
bicellular tight junction
Source: UniProtKB
Inferred from direct assayⁱ
- 23407391
integral component of plasma membrane
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23407391
lateral plasma membrane Source: Ensembl
plasma membrane
Source: UniProtKB
Inferred from direct assayⁱ
- 20375010

Complete GO annotation...

Keywords - Cellular componentⁱ

Cell junction, Cell membrane, Membrane, Tight junction

Pathology & Biotechⁱ

Involvement in diseaseⁱ

CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	208	Y → F: Loss of phosphorylation by EPHA2. 1 Publication		1

Keywords - Diseaseⁱ

Williams-Beuren syndrome

Organism-specific databases

DisGeNET More...DisGeNETⁱ	1364.
Open Targets More...OpenTargetsⁱ	ENSG00000189143.
PharmGKBⁱ	PA26572.

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000144743	1 – 209	Claudin-4Add BLAST		209

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	208	Phosphotyrosine; by EPHA21 Publication		1

Post-translational modificationⁱ

Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.1 Publication

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

EPDⁱ	O14493.
PaxDbⁱ	O14493.
PeptideAtlas More...PeptideAtlasⁱ	O14493.
PRIDEⁱ	O14493.

PTM databases

iPTMnetⁱ	O14493.
PhosphoSitePlusⁱ	O14493.

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000189143.
CleanExⁱ	HS_CLDN4.
ExpressionAtlasⁱ	O14493. baseline and differential.
Genevisibleⁱ	O14493. HS.

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB002610.

HPAⁱ

CAB002610.

Interactionⁱ

Subunit structureⁱ

Directly interacts with TJP1/ZO-1 (PubMed:16236711). Interacts with TJP2/ZO-2 and TJP3/ZO-3 (By similarity). Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions (PubMed:16236711). Interacts with CLDN1 (PubMed:20375010).By similarity2 Publications

GO - Molecular functionⁱ

identical protein binding Source: UniProtKB

Complete GO annotation...

Protein-protein interaction databases

BioGridⁱ	107756. 2 interactors.
IntActⁱ	O14493. 3 interactors.
STRINGⁱ	9606.ENSP00000342445.

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Show more details

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	1 – 3	Combined sources	3
Helixⁱ	7 – 26	Combined sources	20
Beta strandⁱ	30 – 35	Combined sources	6
Beta strandⁱ	44 – 48	Combined sources	5
Beta strandⁱ	50 – 61	Combined sources	12
Beta strandⁱ	63 – 66	Combined sources	4
Helixⁱ	75 – 96	Combined sources	22
Turnⁱ	102 – 106	Combined sources	5
Helixⁱ	117 – 148	Combined sources	32
Beta strandⁱ	154 – 160	Combined sources	7
Helixⁱ	163 – 182	Combined sources	20

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	5B2G	X-ray	3.50	A/C/E/G	1-183	[»]
ProteinModelPortalⁱ	O14493.
SMRⁱ	O14493.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	1 – 103	Interaction with EPHA21 PublicationAdd BLAST		103
Regionⁱ	208 – 209	Interactions with TJP1, TJP2 and TJP3By similarity		2

Sequence similaritiesⁱ

Belongs to the claudin family.Curated

Keywords - Domainⁱ

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	ENOG410IIJR. Eukaryota. ENOG410YA61. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000118928.
HOGENOMⁱ	HOG000220937.
HOVERGENⁱ	HBG000643.
InParanoidⁱ	O14493.
KEGG Orthology (KO) More...KOⁱ	K06087.
OMAⁱ	TAHNVIR.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0MMR.
PhylomeDBⁱ	O14493.
TreeFamⁱ	TF331936.

Family and domain databases

InterProⁱ	View protein in InterPro IPR006187. Claudin. IPR003550. Claudin4. IPR017974. Claudin_CS. IPR004031. PMP22/EMP/MP20/Claudin.
PANTHERⁱ	PTHR12002. PTHR12002. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00822. PMP22_Claudin. 1 hit.
PRINTSⁱ	PR01379. CLAUDIN4.
PROSITEⁱ	View protein in PROSITE PS01346. CLAUDIN. 1 hit.

Sequenceⁱ

Sequence statusⁱ: Complete.

O14493-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MASMGLQVMG IALAVLGWLA VMLCCALPMW RVTAFIGSNI VTSQTIWEGL 
        60         70         80         90        100
WMNCVVQSTG QMQCKVYDSL LALPQDLQAA RALVIISIIV AALGVLLSVV 
       110        120        130        140        150
GGKCTNCLED ESAKAKTMIV AGVVFLLAGL MVIVPVSWTA HNIIQDFYNP 
       160        170        180        190        200
LVASGQKREM GASLYVGWAA SGLLLLGGGL LCCNCPPRTD KPYSAKYSAA 

RSAAASNYV

Length:209

Mass (Da):22,077

Last modified:January 1, 1998 - v1

Checksum:ⁱ0659A93AA5F0E4C5

GO

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AB000712 mRNA. Translation: BAA22984.1. BT006989 mRNA. Translation: AAP35635.1. BC000671 mRNA. Translation: AAH00671.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS5560.1.
NCBI Reference Sequences More...RefSeqⁱ	NP_001296.1. NM_001305.4.
UniGeneⁱ	Hs.647036. Hs.729359.

Genome annotation databases

Ensemblⁱ	ENST00000340958; ENSP00000342445; ENSG00000189143. ENST00000431918; ENSP00000388639; ENSG00000189143. ENST00000435050; ENSP00000409544; ENSG00000189143.
GeneIDⁱ	1364.
KEGGⁱ	hsa:1364.

Similar proteinsⁱ

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:

100%	UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%	UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%	UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Cross-referencesⁱ

Web resourcesⁱ

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AB000712 mRNA. Translation: BAA22984.1. BT006989 mRNA. Translation: AAP35635.1. BC000671 mRNA. Translation: AAH00671.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS5560.1.
NCBI Reference Sequences More...RefSeqⁱ	NP_001296.1. NM_001305.4.
UniGeneⁱ	Hs.647036. Hs.729359.

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	5B2G	X-ray	3.50	A/C/E/G	1-183	[»]
ProteinModelPortalⁱ	O14493.
SMRⁱ	O14493.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	107756. 2 interactors.
IntActⁱ	O14493. 3 interactors.
STRINGⁱ	9606.ENSP00000342445.

Protein family/group databases

TCDBⁱ	1.H.1.1.6. the claudin tight junction (claudin1) family.

TCDBⁱ

1.H.1.1.6. the claudin tight junction (claudin1) family.

PTM databases

iPTMnetⁱ	O14493.
PhosphoSitePlusⁱ	O14493.

Proteomic databases

EPDⁱ	O14493.
PaxDbⁱ	O14493.
PeptideAtlas More...PeptideAtlasⁱ	O14493.
PRIDEⁱ	O14493.

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	1364.
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000340958; ENSP00000342445; ENSG00000189143. ENST00000431918; ENSP00000388639; ENSG00000189143. ENST00000435050; ENSP00000409544; ENSG00000189143.
GeneIDⁱ	1364.
KEGGⁱ	hsa:1364.

Organism-specific databases

CTDⁱ	1364.
DisGeNET More...DisGeNETⁱ	1364.
GeneCardsⁱ	CLDN4.
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:2046. CLDN4.
Human Protein Atlas More...HPAⁱ	CAB002610.
MIMⁱ	602909. gene.
neXtProtⁱ	NX_O14493.
Open Targets More...OpenTargetsⁱ	ENSG00000189143.
PharmGKBⁱ	PA26572.
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410IIJR. Eukaryota. ENOG410YA61. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000118928.
HOGENOMⁱ	HOG000220937.
HOVERGENⁱ	HBG000643.
InParanoidⁱ	O14493.
KEGG Orthology (KO) More...KOⁱ	K06087.
OMAⁱ	TAHNVIR.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0MMR.
PhylomeDBⁱ	O14493.
TreeFamⁱ	TF331936.

Enzyme and pathway databases

Reactomeⁱ	R-HSA-420029. Tight junction interactions.

Reactomeⁱ

R-HSA-420029. Tight junction interactions.

Miscellaneous databases

ChiTaRSⁱ	CLDN4. human.
GeneWikiⁱ	CLDN4.
GenomeRNAiⁱ	1364.
Protein Ontology More...PROⁱ	PR:O14493.
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000189143.
CleanExⁱ	HS_CLDN4.
ExpressionAtlasⁱ	O14493. baseline and differential.
Genevisibleⁱ	O14493. HS.

Family and domain databases

InterProⁱ	View protein in InterPro IPR006187. Claudin. IPR003550. Claudin4. IPR017974. Claudin_CS. IPR004031. PMP22/EMP/MP20/Claudin.
PANTHERⁱ	PTHR12002. PTHR12002. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00822. PMP22_Claudin. 1 hit.
PRINTSⁱ	PR01379. CLAUDIN4.
PROSITEⁱ	View protein in PROSITE PS01346. CLAUDIN. 1 hit.
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CLD4_HUMAN
Accessionⁱ	O14493Primary (citable) accession number: O14493
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
	Last sequence update:	January 1, 1998
	Last modified:	July 5, 2017
	This is version 147 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - O14493 (CLD4_HUMAN)

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Claudin-4

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequenceⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ